Targeting cell surface β2-microglobulin by pentameric IgM antibodies

Yabing Cao, Yongsheng Lan, Jianfei Qian, Yuhuan Zheng, Sungyoul Hong, Haiyan Li, Michael Wang, Larry W. Kwak, Dongyu Lin, Jing Yang, Qing Yi

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Monoclonal antibodies (mAbs) specific for human β2-microglobulin (β2M) have been shown to induce tumour cell apoptosis in haematological and solid tumours via recruiting major histocompatibility complex (MHC) class I molecules into and excluding cytokine receptors from the lipid rafts. Based on these findings, we hypothesized that IgM anti-β2M mAbs might have stronger apoptotic effects because of their pentameric structure. Our results showed that, compared with IgG mAbs, IgM anti-β2M mAbs exhibited stronger tumouricidal activity in vitro against different tumour cells, including myeloma, mantle cell lymphoma, and prostate cancer, and in vivo in a human-like xenografted myeloma mouse model without damaging normal tissues. IgM mAb-induced apoptosis is dependent on the pentameric structure of the mAbs. Disrupting pentameric IgM into monomeric IgM significantly reduced their ability to induce cell apoptosis. Monomeric IgM mAbs were less efficient at recruiting MHC class I molecules into and exclusion of cytokine receptors from lipid rafts, and at activating the intrinsic apoptosis cascade. Thus, we developed and validated the efficacy of anti-β2M IgM mAbs that may be utilized in the clinical setting and showed that IgM anti-β2M mAbs may be more potent than IgG mAbs at inducing tumour apoptosis.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalBritish Journal of Haematology
Volume154
Issue number1
DOIs
StatePublished - Jul 2011

Keywords

  • Anti-β mAbs
  • Haematological and solid tumours
  • IgM pentamer
  • Multiple myeloma
  • Tumour apoptosis

ASJC Scopus subject areas

  • Hematology

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